Hebbian and homeostatic plasticity mechanisms are segregated in sub-types of layer 5 neuron in the visual cortex

Cortical layer 5 contains two major types of projection neuron known as IB (intrinsic bursting) cells that project sub-cortically and RS (regular spiking) cells that project between cortical areas. We studied the plasticity properties of RS and IB cells in the visual cortex during the critical period for ocular dominance plasticity in mice. RS neurons exhibited synaptic depression in response to both dark exposure (DE) and monocular deprivation (MD), and their homeostatic recovery from depression was dependent on TNF. In contrast, IB cells demonstrated opposite responses to DE and MD, potentiating to DE and depressing to MD. IB cells potentiation depended on CaMKII-autophosphorylation and not TNF. IB cells showed mature synaptic properties at the start of the critical period while RS cells matured during the critical period. Together with observations in somatosensory cortex, these results suggest that differences in RS and IB plasticity mechanisms are a general cortical property. Significance StatementThe neocortex contains cells that project to different locations in the brain. In this study we show that neurons projecting to different target locations exhibit different synaptic plasticity mechanisms. Cortically projecting cells show synaptic depression and homeostatic up-regulation, subcortically projecting cells show classical Hebbian potentiation. This is important because it implies that the way a cortical neuron responds to experience and encodes information depends on the neuronal subcircuits in which it is embedded. We show that ignoring this distinction leads to erroneous conclusions regarding plasticity time-course and significance. These findings constitute an important step toward understanding how learning and memory is organized within subcircuits in the cerebral cortex.